Association of a specific chromosomal abnormality with tumor type is established and may reflect of oncogenesis peculiar to that tumor. Alternatively, it way be that these associations reflect the particular differentiated state of the malignant cell, consistent with the model that rearrangements occur only within chromatin in an "active" configuration. We have found that this second possibility has provided a premise and profitable strategy for the identification of genes important to the growth or development of lymphocytes. Our focus this year has followed from our cloning and characterization of two distinctive translocations associated with clonal proliferations of lymphocytes. We discovered the gene, SCL, because of its disruption by a translocation in the malignant cells of a patient suffering from a leukemia with the capability of lymphoid, myeloid, or erythroid, differentiation. We have delineated the genomic and cDNA structures corresponding to both the normal and translocated SCL genes. We have found that SCL is a of a family of genes, each a known or putative transcription factor that plays a fundamental role in the particular developmental systems in which it is expressed. SCL is a transcriptionally complex locus. It is now recognized that chromosomal aberrations disrupt the SCL gene with relative frequency, and in so doing cause a structural or functional abrogation of the gene's normal regulation.